A Copernican revolution of multigenic analysis: A retrospective study on clinical exome sequencing in unclear genetic disorders.

Despite the inevitable shift in medical practice towards a deeper understanding of disease etiology and progression through multigenic analysis, the profound historical impact of Mendelian diseases cannot be overlooked. These diseases, such as cystic fibrosis and thalassemia, are characterized by a single variant in a single gene leading to clinical conditions, and have significantly shaped our medical knowledge and treatments. In this respect, the monogenic approach inevitably results in the underutilization of Next-Generation Sequencing (NGS) data. Herein, a retrospective study was performed to assess the diagnostic value of the clinical exome in 32 probands with specific phenotypic characteristics (patients with autoinflammation and immunological dysregulation, N = 20; patients diagnosed with Hemolytic uremic syndrome N = 9; and patients with Waldenström macroglobulinemia, N = 3). A gene enrichment analysis was performed using the *. VCF file generated by SOPHiA-DDM-v4. This analysis selected a subset of genes containing pathogenic or likely pathogenic variants with autosomal dominant (AD) inheritance. In addition, all variants of uncertain significance (VUS) were included, filtered by AD inheritance mode, the presence of compound heterozygotes, and a minor allele frequency (MAF) cutoff of 0.05 %. The aim of the pipeline described here is based on a perspective shift that focuses on analyzing patients' gene assets, offering new light on the complex interplay between genetics and disease presentation. Integrating this approach into clinical practices could significantly enhance the management of patients with rare genetic disorders.

[What about the weekend effect? Impact of the day of admission on in-hospital mortality, length of stay and cost of hospitalization]. / ¿Qué hay del efecto fin de semana? Impacto del día de ingreso sobre la mortalidad intrahospitalaria, la duración de la estancia y el coste de la hospitalización.

INTRODUCTION: There is no agreement on the existence of the weekend effect in healthcare or, if it exists, on its possible causes. The objective of the study was to evaluate the differences in healthcare outcomes between patients admitted on weekdays or weekends in a high-complexity hospital. METHODS: Observational and retrospective study of patients admitted between 2016 and 2019 in a public hospital with more than 1300 beds. Hospitalization episodes were classified according to whether admission took place between Friday at 3:00 p.m. and the following Monday at 8:00 a.m. (weekend admission) or not (admission on weekdays). Mortality, length of stay and associated costs were compared, applying their respective risk-adjustment models. RESULTS: Of the total 169,495 hospitalization episodes analyzed, 48,201 (28.44%) corresponded to the weekend, presenting an older age (54.9 years vs. 53.9; P<.001), a higher crude mortality rate (5.22% vs. 4.59%; P<0.001), and a longer average length of stay (7.42 days vs. 6.74; P<.001), than those admitted on weekdays. The median crude cost of stay was lower (€731.25 vs. €850.88; P<0.001). No significant differences were found when applying the adjustment models, with a risk-adjusted mortality ratio of 1.03 (0.99-1.08) vs. 0.98 (0.95-1.01), risk-adjusted length of stay of 1.002 (0.98-1.005) vs. 0.999 (0.997-1.002) and risk-adjusted cost of stay of 0.928 (0.865-0.994) vs. 0.901 (0.843-0.962). CONCLUSION: The results of the study reveal that the assistance provided during the weekends does not imply worse health outcomes or increased costs. Comparing the impact between hospitals will require a future homogenization of temporal criteria and risk adjustment models.

[Multidisciplinary approach for deep endometriosis: interests and organization]. / Réunion de concertation pluridisciplinaire de l'endométriose pelvienne profonde : intérêts et modalités de fonctionnement.

Deep endometriosis is a frequent disease that affects reproductive age women. This disease is characterized by the presence of functional endometrium-like tissue outside the uterus. The common sites of extragenital endometriosis are the bowel and the urinary tract. This disease is also associated with infertility. Furthermore, this disease can cause physical and psychological damage. Therefore, it is really important to develop a multidisciplinary approach in the aim to offer the appropriate treatment. The multidisciplinary team approach for endometriosis is developing to improve the understanding of endometriosis and a multidisciplinary committee for endometriosis was developed in our center. During this meeting, gynecologic, digestive surgeons, urologist, radiologist, procreative medical assistance physicians analyse the case. The role of surgery, before, after or as an alternative to in vitro fertilization (IVF) must be defined. The role of the medical treatment before or after the surgery, before the IVF shall be discussed in order to propose the optimal treatment. In fact, radical surgery is no more recommended and minimally invasive conservative surgery is encouraged in order to preserve the fertility. The multidisciplinary approach permits an appropriate optimal and personalised management of this multifocal disease. The multidisciplinary team approach helps in the development of evidence-based guidelines for the diagnosis and management of endometriosis.

Estudio del polimorfismo del gen de TNF-α, de dicha citocina, y de MCP-1 en pacientes con queratopatía climática esferoidea / Studies of TNF-α gene polymorphism, TNF-α and MCP-1 cytokines in patients with spheroidal climatic keratopathy

Objetivo. Investigar polimorfismo de nucleótidos únicos (SNP) en la posición -308 (G/A) del gen TNF-α y la participación de las citocinas TNF-α y MCP-1 en pacientes con queratopatía climática esferoidea (QCE) y en controles sanos. Materiales y métodos. Participaron 15 pacientes con QCE y 15 individuos sanos del departamento El Cuy, Provincia de Río Negro. Todos ellos, luego de firmar el consentimiento informado, recibieron un examen oftalmológico completo y se recolectaron muestras de sangre y lágrima para realizar diferentes estudios. EL ADN genómico fue obtenido de sangre de todos los individuos mediante el método de salting out y posteriormente amplificado y estudiado mediante reacción en cadena de la polimerasa (PCR) con el sistema de amplificación refractaria a la mutación (ARMS). También se investigaron concentraciones de algunas citocinas proinflamatorias en lágrimas y en sobrenadante de cultivo de células epiteliales corneales humanas (CECH) tratadas o no con radiación ultravioleta B (RUV-B). Resultados. Los resultados de SNP en la posición -308 (G/A) del gen TNF-α (frecuencia alélica y genotípica) indicaron ausencia de diferencias significativas entre pacientes y controles sanos. Fenotípicamente ambos grupos de individuos serían bajos o intermedios productores in vitro de la citocina TNF-α. Sin embargo en las lágrimas de pacientes con QCE se detectaron concentraciones significativamente superiores de TNF-α, IL-1ß y MCP-1 (citocinas proinflamatorias) que en lágrimas de individuos controles sanos (p<0,0001) En la periferia y limbo de la córnea las células dendríticas (CD) incrementaron significativamente con el progreso de la enfermedad (p<0,05). La contribución del epitelio corneal en el proceso inflamatorio fue investigada utilizando CECH expuestas o no a 10 mJ/cm2 de RUV-B. A pesar de la presencia de gelatinasas, IL-6 e IL-8 en sobrenadantes de cultivos obtenidos a las 48 horas (datos no mostrados) no observamos niveles detectables de TNF-α, IL-1ß ni MCP-1. Conclusión. Este trabajo aporta nuevos datos para aumentar los conocimientos sobre los mecanismos inmunológicos involucrados en la etiopatogenia y progresión de la QCE. Demostramos que las citocinas proinflamatorias MCP-1 y TNF-α están significativamente elevadas en lágrimas de individuos con QCE, como se observó previamente con IL-1ß. MCP-1 sería la responsable del aumento de CD en córnea periférica y limbo de estos pacientes a medida de que la enfermedad avanza. El hallazgo de que estas citocinas no pudieron ser detectadas en cultivos de CECH estresadas con RUV-B implica que otras células son las responsables de su producción o que además de RUV-B otros factores son necesarios para iniciar esta cascada de eventos que se observan en esta hipersensibilidad corneal humana(AU)

Purpose. To investigate Single Nucleotide Polymorphism (SNP) at -308 position (G/A) of TNF-α gen and involving of TNF-α and MCP-1 cytokines in Climatic Droplet Keratopathy (CDK) patients and healthy controls. Materials and methods. Fifteen patients with CDK and fifteen healthy controls from departamento El Cuy, province of Rio Negro were involved in this study. After informed consent was obtained from all participants, they had a complete eye examination and then tear and blood samples were collected to perform different assays. DNA was obtained from blood of all individuals using the method of "salting out" and then amplified and studied performing the polymerase chain reaction (PCR) with Amplification-refractory Mutation System (ARMS). Furthermore, some cytokines concentrations were measured in tears and supernatants from human corneal epithelial cells (HCEs) exposed or not to UVR-B radiation. Results. Analysis from SNP at position -308 (G/A) of TNF-α gen (allelic and genotypic frequency) showed no significant differences between patients and healthy controls. Phenotypically both groups of individuals would be low or intermediate in vitro producers of TNF-α cytokine. However, in tears from CDK's patients we detected significantly higher concentrations of TNF-α, IL-1ß and MCP-1 (pro-inflammatory cytokines) than in healthy control subjects tears (p<0.0001). At the corneal peripheral / limbus area, dendritic cells (DCs) increased significantly with the progression of the disease (p<0.05). The corneal epithelium contribution to the inflammatory process was investigated using HCEs exposed or not to 10 mJ/cm2 of UV radiation­B (UVR-B). Despite the presence of gelatinases, IL-6 and IL-8 in culture supernatants obtained after 48 hours (data not shown), detectable levels of TNF-α, IL-1ß and MCP-1 were not detected. Conclusion. This study provides new insights to increase our knowledge about the immunological mechanisms involved in the etiopathogenesis and progression of CDK. We showed that pro-inflammatory cytokines MCP-1 y TNF-α were significantly increased in tears from CDK's patients, as previously described with IL-1ß. MCP-1 would be responsible for the increasing of DCs on the corneal peripheral / limbus area of these subjects as the disease progresses. The fact that these cytokines could not be detected in cultures of HCEs stressed with UVR-B implies that other cells are responsible for their production or, in addition to UVR-B, other factors are necessary to initiate the cascade of events observed in this human corneal hypersensitivity. (AU)

Encuesta sobre el conocimiento y manejo de los pacientes con ataque isquémico transitorio entre médicos y enfermería de Atención Primaria / Survey of the knowledge and management of transient ischemic attacks among primary care physicians and nurses

Introducción: La principal fuente de consulta de los pacientes con ataque isquémico transitorio (AIT) agudo en nuestra área sanitaria son los centros de salud de Atención Primaria. Existen muy pocos estudios sobre el conocimiento del AIT y su manejo entre profesionales de la medicina comunitaria y de familia.Objetivo: Estimar el conocimiento del AIT, su manejo y las pruebas complementarias necesarias entre médicos y personal de enfermería de Atención Primaria de nuestra área de influencia. Para ello se envió una encuesta electrónica cerrada a 640 profesionales con 7 preguntas sobre el AIT.Resultados: Se obtuvo una alta tasa de respuestas: 285 (46,7% médicos). 239 (83,9%) participantes mostraron un conocimiento adecuado de la duración del AIT. Sólo 40 (14%) de la sintomatología. Mientras que el 67% contestó adecuadamente que es necesaria una prueba de neuroimagen urgente. Sólo el 42,5% reconoció la necesidad una exploración con dúplex de troncos supraórticos precoz. Únicamente, el 35,4% conocía qué es un doppler transcraneal, mientras que el 78,2% supo que era más adecuado enviar a estos pacientes a urgencias hospitalarias. El predictor independiente de mejor conocimiento fue ser un médico de Atención Primaria (MAP) (odds ratio [OR]: 2,138; IC 95%: 1,124-4,067; p = 0,021) pero no hubo diferencias entre MAP y enfermería en el conocimiento del manejo de estos pacientes. En enfermería fue peor el conocimiento en el ámbito rural (OR: 0,410; IC 95%: 0,189-0,891; p = 0,024). Conclusión: El conocimiento de la actitud ante un AIT es correcto en la mayoría de casos, sin embargo es necesario mejorar el conocimiento de la sintomatología de los AIT (AU)

Introduction: Transient ischaemic attack (TIA) patients often report that Primary Care physicians(PCPs) and nurses are their main medical contacts after onset of symptoms in our healtharea. There are few studies on the knowledge and management of TIA among Community andFamily Medicine professionals.Material and methods: Our aim was to study the current knowledge and practice in the managementof TIA patients among Primary Care physicians and nurses. A cross-sectional survey withseven questions about TIA was conducted among 640 PCPs and nurses from Primary Care centresin our health area.Results: In total, 285 (46.7% PCPs) took participate in the study. Of these, 239 (83.9%) participantsknew the duration of a TIA. However only 40 (14%) recognised all clinical symptoms.An urgent neuroimaging was preferred by 67%. Only 42.5% agreed that an urgent cervicalduplex would be useful in these patients. Transcranial Doppler was recognised by only 35.4%.A majority (78.2%) of participants agreed that TIA patients must be admitted to hospital. PCPshad the best knowledge of TIA (odds ratio [OR] 2.138; 95% CI 1.124-4.067; P = 0.021) but therewere no differences between physicians and nurses on the management of these patients.Nurses from rural Primary Care centers had the worst level of knowledge (OR 0.410; 95% CI0.189-0.891; P = 0.024).Conclusion: TIA was well recognized as a medical emergency. However, knowledge of clinicalsymptoms of TIA must be improved (AU)

Survey of the knowledge and management of transient ischemic attacks among primary care physicians and nurses.

INTRODUCTION: Transient ischaemic attack (TIA) patients often report that Primary Care physicians (PCPs) and nurses are their main medical contacts after onset of symptoms in our health area. There are few studies on the knowledge and management of TIA among Community and Family Medicine professionals. MATERIAL AND METHODS: Our aim was to study the current knowledge and practice in the management of TIA patients among Primary Care physicians and nurses. A cross-sectional survey with seven questions about TIA was conducted among 640 PCPs and nurses from Primary Care centres in our health area. RESULTS: In total, 285 (46.7% PCPs) took participate in the study. Of these, 239 (83.9%) participants knew the duration of a TIA. However only 40 (14%) recognised all clinical symptoms. An urgent neuroimaging was preferred by 67%. Only 42.5% agreed that an urgent cervical duplex would be useful in these patients. Transcranial Doppler was recognised by only 35.4%. A majority (78.2%) of participants agreed that TIA patients must be admitted to hospital. PCPs had the best knowledge of TIA (odds ratio [OR] 2.138; 95% CI 1.124-4.067; P = 0.021) but there were no differences between physicians and nurses on the management of these patients. Nurses from rural Primary Care centers had the worst level of knowledge (OR 0.410; 95% CI 0.189-0.891; P = 0.024). CONCLUSION: TIA was well recognized as a medical emergency. However, knowledge of clinical symptoms of TIA must be improved.

Guía de buenas prácticas clínicas: asma bronquial en el niño / Guide to good clinical practices: bronchial asthma in children

El Asma Bronquial es la enfermedad crónica no transmisible de mayor prevalencia en la infancia mundialmente y en Cuba por lo que se considera un problema de salud. Su prevalencia ha aumentado en las últimas décadas siendo mal diagnosticada y tratada. Existe desinformación del personal médico, paramédico, enfermos y familiares sobre su prevención, correcto diagnóstico, pronóstico y tratamiento. Por lo que desde el año 2006 el servicio de respiratorio y alergia del Hospital Pediátrico Universitario de Holguín realiza talleres y cursos de capacitación, con el fin de actualizar los conocimientos y unificar criterios en el manejo integral del niño asmático en todos los niveles de atención y de esta forma mejorar la calidad de vida de los mismos, para lo que se elaboró esta Guía de Buenas Prácticas Clínicas.

[Study of the prognostic implications in patients with a transient ischaemic attack before the implementation of an agreed process of treatment in the health region of Lleida]. / Estudio de las implicaciones pronósticas del paciente con ataque isquémico transitorio antes de la implantación de un proceso consensuado de tratamiento en la región sanitaria de Lleida.

AIM: The transient ischemic attack (TIA) is a medical emergency because of their high risk of early recurrence. We study the evolution and management of patients with a TIA in our hospital before establishing a process management and treatment of this condition. PATIENTS AND METHODS: We included 180 consecutive patients with suspected TIA attended in the emergency department of our hospital between January 2006 and March 2007. We collected clinical variables (risk factors, age, clinical symptoms, duration, ABCD2). Cases were reviewed by two neurologists to establish the correlation with the diagnosis. We established the risk of cerebral infarction after one year follow-up. RESULTS: 31% of patients were discharged home. There were differences between the two groups regarding age (82.9 Y 7.5 vs 70.53 Y 10.7 years); ABCD2 scale score (1.5 Y 5.32 vs 4.44 Y 1.37); and atrial fibrillation (27.5% vs 8.6%). There was much greater delay and lack of complementary explorations. During follow-up, 23% of patients not hospitalized had recurrent stroke versus 6.7% of hospitalized patients. Despite the fact that only age more than 80 years was identified as predictor of stroke recurrence (hazard ratio = 8,72; 95% CI = 2.4-31.74; p = 0.001) in regression multivariate model, the Kaplan-Meier model showed a higher risk of stroke recurrence among not admitted patients (p = 0.012). CONCLUSION: In our area, the management of TIA patients in the emergency room had high impact on the evolution of these patients. A process management should be performed in order to achieve improvement in clinical praxis.

Estudio de las implicaciones pronósticas del paciente con ataque isquémico transitorio antes de la implantación de un proceso consensuado de tratamiento en la región sanitaria de Lleida / Study of the prognostic implications in patients with a transient ischaemic attack before the implementation of an agreed process of treatment in the health region of Lleida

Objetivo. Conocer la realidad del manejo y evolución de los pacientes con un ataque isquémico transitorio (AIT) en nuestro centro antes de instaurar un proceso de tratamiento de esta patología. Pacientes y métodos. Estudiamos a 180 pacientes consecutivos que acudieron a urgencias de nuestro centro (entre enero de 2006 y marzo de 2007). Los casos fueron revisados por dos neurólogos para establecer la concordancia con el diagnóstico. Se estableció el riesgo de infarto cerebral tras un seguimiento de un año. Resultados. Hubo discordancia en el diagnóstico de AIT en 40 casos. Un 31% de los pacientes fue dado de alta a su domicilio desde urgencias. Al comparar éstos con los que ingresaron en el servicio de neurología, se observan diferencias en la edad (82,9 ± 7,5 frente a 70,53 ± 10,7 años), puntuación en la escala ABCD2 (5,32 ± 1,5 frente a 4,44 ± 1,37) y fibrilación auricular (27,5% frente a 8,6%). Asimismo, el tiempo para realizar el estudio etiológico fue mucho mayor y el número de exploraciones complementarias mucho menor. Al cabo de un año, el 23% de estos pacientes sufrió un infarto cerebral, por sólo el 6,7% de los hospitalizados en planta en neurología. Pese a que sólo la edad superior a 80 años se comportó como único predictor de recurrencia (razón de riesgo = 8,72; intervalo de confianza al 95% = 2,4-31,74; p = 0,001), el modelo de Kaplan-Meier demuestra la peor evolución del paciente no ingresado (p = 0,012). Conclusión. En nuestra zona, el alta domiciliaria desde urgencias tiene repercusión sobre el peor estudio etiológico y la evolución del enfermo. Se debe establecer un proceso de manejo del AIT consensuado para asegurar el diagnóstico y tratamiento adecuados (AU)

Aim. The transient ischemic attack (TIA) is a medical emergency because of their high risk of early recurrence. We study the evolution and management of patients with a TIA in our hospital before establishing a process management and treatment of this condition. Patients and methods. We included 180 consecutive patients with suspected TIA attended in the emergency department of our hospital between January 2006 and March 2007. We collected clinical variables (risk factors, age, clinical symptoms, duration, ABCD2). Cases were reviewed by two neurologists to establish the correlation with the diagnosis. We established the risk of cerebral infarction after one year follow-up. Results. 31% of patients were discharged home. There were differences between the two groups regarding age (82.9 ± 7.5 vs 70.53 ± 10.7 years); ABCD2 scale score (1.5 ± 5.32 vs 4.44 ± 1.37); and atrial fibrillation (27.5% vs 8.6%). There was much greater delay and lack of complementary explorations. During follow-up, 23% of patients not hospitalized had recurrent stroke versus 6.7% of hospitalized patients. Despite the fact that only age more than 80 years was identified as predictor of stroke recurrence (hazard ratio = 8,72; 95% CI = 2.4-31.74; p = 0.001) in regression multivariate model, the Kaplan-Meier model showed a higher risk of stroke recurrence among not admitted patients (p = 0.012). Conclusion. In our area, the management of TIA patients in the emergency room had high impact on the evolution of these patients. A process management should be performed in order to achieve improvement in clinical praxis (AU)

Predictive value of ankle brachial index in patients with acute ischaemic stroke.

BACKGROUND: The ankle brachial index (ABI) is a known measure of lower-limb peripheral artery disease (PAD), as well as a marker for other cardiovascular disease events. OBJECTIVE: Our goal was to compare the prevalence of abnormal ABI scores (ABI or=3 (33.8% vs. 7.1%, P = 0.001) and large-artery atherosclerosis (LAA) (43.5% vs. 19.4%, P = 0.015). Multivariate analyses (logistic regression) only identified VRF > 3 as independently associated with low ABI (OR: 6.46; 1.81-23.02; P = 0.004). Abnormal ABI was associated with stroke recurrence (32.1% vs. 13.6%, P = 0.027) and the appearance of any major vascular event (50.0% vs. 17.0%, P < 0.001). In the logistic regression analysis, adjusted for VRF, age, and LAA, ABI remained as an independent predictor of vascular events (HR 3.99; 1.90-8.41 P < 0.001). CONCLUSION: Abnormal ABI was associated with classical risk factors, especially hypertension. The measurement of ABI amongst patients with IS appeared to be useful to identify high-risk patients and plan adequate prevention therapies.

[The extent of knowledge about strokes among the population of a rural area in the province of Lleida]. / Grado de conocimiento del ictus entre poblacion de area rural en la provincia de Lleida.

INTRODUCTION: Although stroke continues to be a significant cause of morbidity and mortality, the knowledge of warning signs and risk factors among general population is still insufficient. AIM: To assess the current knowledge of stroke (terminology, signs and symptoms, risk factors and attitude) among rural population of Baix Segria in Lleida in order to the best target and message, prior to educational campaigns. SUBJECTS AND METHODS: A structured interview using closeended questions was conducted among 153 users of Primary Health Centers. RESULTS: In our cohort, 6.5% ignored the disease, while 48 (31,4%) had good knowledge of risk factors (more than three risk factors) and 62 (40,5%) identified more than three warnings signs correctly. Only 31,1% would correctly act if stroke occurred. Transient ischemic attack was not considered as emergency. Most participants, 78,5%, would contact to primary care. Surprisingly, knowledge of stroke symptoms and risk factors was not associated with an increased chance of calling 061 or going to the hospital. Older respondents were less likely to recognize symptoms and to consider stroke as an emergency, while the university education was associated with good knowledge and actuation. CONCLUSION: The level of knowledge of established stroke risk factors, warning signs, and treatment in rural population of Lleida is low. Our data suggested not only that a community-based education program to increase public knowledge of stroke among rural population is necessary, but also we need to inform the people stroke is treatable.

Grado de conocimiento del ictus entre población de área rural en la provincia de Lleida / The extent of knowledge about strokes among the population of a rural area inthe province of lleida

Introducción. Pese a que el ictus es la principal causa de discapacidad y una de las principales causas de muerte, el conocimiento de sus síntomas, sus causas y de la existencia del tratamiento fibrinolítico es escaso en la población general. Objetivo. Establecer el grado de conocimiento del ictus (terminología, factores de riesgo, síntomas y actitud) en el área rural de Lleida (Baix Segrià). Sujetos y métodos. Estudio de población mediante cuestionario cerrado realizado de forma aleatoria en tres centros de salud sobre un total de 153 sujetos. Resultados. Un 6,5% desconoce completamente la enfermedad. El término ‘ictus’ sólo lo reconoce el 26,7%, y el término ‘embolia’, el 86,9%. Veinte personas reconocen más de siete términos. Hay un buen conocimiento de los factores de riesgo (más de cuatro factores de riesgo y menos de dos distractores) en sólo 25 (16,3%) encuestados. El síntoma más reconocido es la alteración del habla (70,6%). El conocimiento de los síntomas es óptimo (más de cuatro síntomas y menos de dos distractores) en 32 (20,9%). El 68%, en caso de ictus, avisaría primero al médico de cabecera. Si se tratase de un ataque isquémico transitorio, el 84,5% acudiría primero al médico de cabecera; de ellos, el 27% no de forma urgente. Los encuestados con estudios universitarios son los que mejor conocen los factores de riesgo y los síntomas, y los que mejor actúan frente a un ictus (p < 0,05). Los mayores de 65 años son los que peor conocimiento tienen de la enfermedad. Conclusión. El conocimiento de la enfermedad es insatisfactorio en el área rural de Lleida. Son necesarias campañas de información a la población general para mejorar la implantación del Código Ictus en esta zona (AU)

Introduction. Although stroke continues to be a significant cause of morbidity and mortality, the knowledge of warning signs and risk factors among general population is still insufficient. Aim. To assess the current knowledge of stroke (terminology, signs and symptoms, risk factors and attitude) among rural population of Baix Segrià in Lleida in order to the best target and message, prior to educational campaigns. Subjects and methods. A structured interview using closeended questions was conducted among 153 users of Primary Health Centers. Results. In our cohort, 6.5% ignored the disease, while 48 (31,4%) had good knowledge of risk factors (more than three risk factors) and 62 (40,5%) identified more than three warnings signs correctly. Only 31,1% would correctly act if stroke occurred. Transient ischemic attack was not considered as emergency. Most participants, 78,5%, would contact to primary care. Surprisingly, knowledge of stroke symptoms and risk factors was not associated with an increased chance of calling 061 or going to the hospital. Older respondents were less likely o recognize symptoms and to consider stroke as an emergency, while the university education was associated with good knowledge and actuation. Conclusion. The level of knowledge of established stroke risk factors, warning signs, and treatment in rural population of Lleida is low. Our data suggested not only that a community-based education program to increase public knowledge of stroke among rural population is necessary, but also we need to inform the people stroke is treatable (AU)

[Detection of silent peripheral arterial disease in stroke patients with a low ankle-arm index]. / Detección mediante el índice tobillo-brazo de enfermedad arterial periférica silente en pacientes con ictus isquémico.

INTRODUCTION: A low ankle-arm index (AAI) is a strong predictor of vascular events and stroke. Nevertheless few studies have prospectively determined AAI in stroke patients. We aimed to investigated the prevalence of low AAI in stroke patients and which variables are associated with abnormal AAI. METHODS: Clinical data and ultrasonographic findings were collected in 79 consecutive stroke patients (20 transient ischemic attacks and 59 cerebral < ischemic infarction). During admission, AAI was measured in all subjects with the Doppler. An AAI cutoff of 0.90 was used to categorize individuals (< or =0.90: abnormal). RESULTS: A low AAI was calculated in 16 (20.3%) patients. AAI < or = 0.90 was associated with hypertension, smoking, hypercholesterolemia, coronary disease, previous peripheral arterial disease, male gender, internal carotid stenosis>50% (p<0.10). The presence of peripheral artery disease varied between subtypes. The incidence was higher for large artery atherosclerosis, 25.0 % and small vessel disease (31.5%). Multivariate analyses (logistic regression) only identify the association of>3 risk factors as independent predictor of low AAI (odds ratio: 4.41; confidence interval 95%: 1.39-4.01; p=0.012). CONCLUSION: Stroke patients had higher incidence of low AAI. Abnormal AAI was associated with classical risk factors. Existence of silent peripheral arterial disease in these patients may be an indicator of cerebral atherosclerosis extension. The measurement of AAI may be useful in order to plan adequate prevention therapies.

Detección mediante el índice tobillo-brazo de enfermedad arterial periférica silente en pacientes con ictus isquémico / Detection of silent peripheral arterial disease in stroke patients with a low ankle-arm index

Introducción. Un índice tobillo-brazo bajo (ITB) es un predictor de episodios vasculares, entre ellos los isquémicos cerebrales. Pese a ello casi no existen estudios sobre la incidencia de ITB anormales en pacientes con ictus isquémico. El objetivo del estudio es determinar la prevalencia y las variables clínicas asociadas a ITB bajo. Métodos. Estudiamos de forma consecutiva a 79 pacientes con un ictus isquémico (20 ataques isquémicos transitorios y 59 infartos cerebrales). Se recogieron datos clínicos y ultrasonográficos. Durante el ingreso se determinó mediante doppler el ITB. Se consideró como patológico un ITB <= 0,9. Resultados. Se observó un ITB<=0,9 en 16 (20,3 %) casos. El ITB patológico se asoció a antecedentes de hipertensión arterial, tabaquismo, dislipemia, cardiopatía isquémica, enfermedad arterial periférica, sexo varón y estenosis carotídea >50% (p < 0,10). El ITB bajo fue más frecuente en pacientes con ictus lacunar (31,5 %) o ateromatoso (25,0 %). En el análisis multivariante (regresión logística) la acumulación de más de tres factores de riesgo vascular se comportó como único predictor independiente de ITB <= 0,9 (odds ratio: 4,41; intervalo de confianza del 95 %: 1,39-14,01; p = 0,012). Conclusión. Existe un alto porcentaje de ITB bajo en pacientes con ictus isquémico. El ITB patológico se asocia a la presencia de factores de riesgo vascular clásicos. La existencia de enfermedad arterial periférica silente en estos pacientes podría traducir una extensión del proceso aterosclerótico cerebral. La determinación del ITB podría condicionar la elección del tratamiento de prevención secundaria más adecuado

Introduction. A low ankle-arm index (AAI) is a strong predictor of vascular events and stroke. Nevertheless few studies have prospectively determined AAI in stroke patients. We aimed to investigated the prevalence of low AAI in stroke patients and which variables are associated with abnormal AAI. Methods. Clinical data and ultrasonographic findings were collected in 79 consecutive stroke patients (20 transient ischemic attacks and 59 cerebral < ischemic infarction). During admission, AAI was measured in all subjects with the Doppler. An AAI cutoff of 0.90 was used to categorize individuals (<=0.90: abnormal). Results. A low AAI was calculated in 16 (20.3%) patients. AAI <= 0.90 was associated with hypertension, smoking, hypercholesterolemia, coronary disease, previous peripheral arterial disease, male gender, internal carotid stenosis>50% (p<0.10). The presence of peripheral artery disease varied between subtypes. The incidence was higher for large artery atherosclerosis, 25.0 % and small vessel disease (31.5%). Multivariate analyses (logistic regression) only identify the association of>3 risk factors as independent predictor of low AAI (odds ratio: 4.41; confidence interval 95%: 1.39-4.01; p=0.012). Conclusion. Stroke patients had higher incidence of low AAI. Abnormal AAI was associated with classical risk factors. Existence of silent peripheral arterial disease in these patients may be an indicator of cerebral atherosclerosis extension. The measurement of AAI may be useful in order to plan adequate prevention therapies

Quantitative assessment of minimal residual disease in acute myeloid leukemia carrying nucleophosmin (NPM1) gene mutations.

Mutations in exon 12 of the nucleophosmin (NPM1) gene occur in about 60% of adult AML with normal karyotype. By exploiting a specific feature of NPM1 mutants, that is insertion at residue 956 or deletion/insertion at residue 960, we developed highly sensitive, real-time quantitative (RQ) polymerase chain reaction (PCR) assays, either in DNA or RNA, that are specific for various NPM1 mutations. In all 13 AML patients carrying NPM1 mutations at diagnosis, cDNA RQ-PCR showed >30 000 copies of NPM1-mutated transcript. A small or no decrease in copies was observed in three patients showing partial or no response to induction therapy. The number of NPM1-mutated copies was markedly reduced in 10 patients achieving complete hematological remission (five cases: <100 copies; five cases: 580-5046 copies). In four patients studied at different time intervals, the number of NPM1 copies closely correlated with clinical status and predicted impending hematological relapse in two. Thus, reliable, sensitive RQ-PCR assays for NPM1 mutations can now monitor and quantify MRD in AML patients with normal karyotype and NPM1 gene mutations.

Peru-15, an improved live attenuated oral vaccine candidate for Vibrio cholerae O1.

Cholera vaccine candidate Peru-15 was derived from a Vibrio cholerae O1 El Tor Inaba strain by deleting the cholera toxin genetic element, introducing the gene encoding cholera toxin B subunit into recA, and screening for nonmotility. In a controlled study, Peru-15 (2 x 10(8) cfu) was administered to 11 volunteers. No vaccinee developed diarrhea, and 10 of 11 had > 4-fold rises in vibriocidal antibody titers. One month later, 5 vaccinees and 5 control volunteers were challenged with wild type V. cholerae O1. Four of 5 controls developed diarrhea (mean, 1.9 L). Two Peru-15 vaccinees developed diarrhea, 1 with < 0.3 L and 1 with approximately 1.0 L; this latter volunteer had not developed a significant vibriocidal immune response to vaccination. Peru-15 shows promise as a single-dose, oral cholera vaccine that is safe, immunogenic, and protective.